TP53 Regulates Transcription of Cell Death Genes (Homo sapiens)

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1, 3, 4, 8, 10...7, 1043, 36, 58, 60, 93...28, 30, 698537, 52, 654, 21, 29, 4118, 51, 8932817620, 719, 13, 15, 37, 6476242178844, 993340, 488, 44, 57, 69, 733325, 677181, 10225, 67, 82, 8749, 62889881124, 35, 44, 9061, 1005030, 55, 69128, 30, 6995891046, 81, 1028, 44, 57, 69, 7354, 75, 1037812, 32, 9448647666, 7075987816, 10083, 85, 9592, 9548, 7921, 4117425, 10230, 55, 693, 58, 60, 971044, 9914, 53, 66, 77, 86724, 35, 44, 9013, 22, 37, 43, 52...cytosolmitochondrionmitochondrial matrixendosome membranenucleoplasmIGFBP3TP63 TP53AIP1TNFRSF10D Gene p-S15,S20-TP53Tetramer:IGFBP3GeneBAX Genep-T788-PIDD1ATPApoptotic execution phasePPP1R13B p-S15,S20-TP53Tetramer:NDRG1 GenePMAIP1 Gene p-S15,S20-TP53 p-S15,S20,S46-TP53 BID Gene ZNF420:TP53AIP1 Genep-S15,S20,S46-TP53Tetramer:TP53AIP1Genep-S15,S20,S46-TP53 TP53AIP1 GeneBAX Gene p-S15,S20-TP53,TP63Regulation of TP53Activityp-S15,S20-TP53Tetramer:BCL2L14GeneBIRC5 GeneTP53INP1 GeneNLRC4STEAP3 AIFM2O2.-p-S15,S20-TP53 ZNF420AIFM2 GeneBNIP3L Gene PRELID1 BCL2L14 Gene TP53I3 DimerSTEAP3:BNIP3LRABGGTA semiquinonePPP1R13B TNFRSF10D CRADD TP73 TP53INP1 Gene PMAIP1TNFRSF10C Gene Interleukin-1processingTNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10D Genesp-S15,S20-TP53 TNFRSF10D Gene p-T788-PIDD1 IGFBP3:TMEM219TP53I3 GeneCHMPPP1R13B p-S15,S20-TP53Tetramer:PMAIP1GeneRABGGTA BCL2L14 Genep-S15,S20-TP53 CRADD p-S15,S20-TP53 p-S15,S20-TP53TetramerTP53BP2 p-S15,S20-TP53 PATP73 p-S15,S20-TP53 p-S15,S20-TP53 APAF1Intrinsic Pathwayfor Apoptosisp-S15,S20-TP53Tetramer:CASP10Genep-S15,S20-TP53 PERP GeneTP63 p-S15,S20-TP53 TP53AIP1 Gene TP73 ATPp-S15,S20-TP53 TNFRSF10B Gene CREBBP PERP Gene RABGGTBNADP+STEAP3 Gene O2phosphatidic acidZNF420 p-S68-ZNF420PPP1R13B CASP2(2-452)BIRC5 Gene (p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):BAX GeneBBC3 Gene APAF1 GenePMAIP1 Genep-S15,S20-TP53Tetramer:BCL6 GeneTP53INP1ADPFASp-S15,S20-TP53 (p-S15,S20-TP53,TP63):PERP GeneTMEM219BID Genep-S15,S20-TP53 p-S15,S20-TP53Tetramer:APAF1 GeneTNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10DTRIAP1:PRELID1p-S15,S20-TP53Tetramer:STEAP3GeneCASP2(2-452) p-S15,S20-TP53Tetramer:TNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10D GenesTMEM219 p-T788-PIDD1(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):BBC3 Genep-S15,S20-TP53 TP63 CASP2(170-325)p-S15,S20-TP53,TP63,TP73CASP6 GeneBNIP3L GeneTP73 CASP6 Gene CREBBPp-S15,S20-TP53Tetramer:PIDD1 GeneBAXTRIAP1 Gene p-S15,S20-TP53 PRELID1FAS GeneBCL6(p-S15,S20-TP53,TP63,TP73):CASP1 Genep-S15,S20-TP53 ADPp-S15,S20-TP53:NLRC4GeneBCL6 Gene TP63 BCL6 GeneFasL/ CD95LsignalingIron uptake andtransportTP53AIP1 Gene TNFRSF10B Gene RGGT:CHMp-S15,S20-TP53 p-S15,S20-TP53 RABGGTA Gene Regulation ofInsulin-like GrowthFactor (IGF)transport anduptake byInsulin-like GrowthFactor BindingProteins (IGFBPs)TRIAP1 Genep-S15,S20-TP53Tetramer:BID GeneH+NLRC4 Genep-S15,S20-TP53 (p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2)p-S15,S20-TP53 TP53BP2 p-S15,S20-TP53Tetramer:RABGGTAGenePPP1R13B STEAP3 GeneTP53I3 Gene p-S15,S20-TP53Tetramer:AIFM2 Genep-S15,S20-TP53 p-S15,S20-TP53 RABGGTB CASP10 Gene PIDDosome:CASP2(2-452)p-S15,S20-TP53Tetramer:BIRC5 Gene(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):TP53I3 GeneTP73 BBC3 GenePERPAPAF1 Gene p-S15,S20-TP53 TP63 BNIP3L RABGGTA GeneIGFBP3 GeneTP73 CASP1(1-404)NADPHp-T788-PIDD1 1,2-NaphthoquinoneInnate Immune SystemTNFRSF10C p-S15,S20-TP53Tetramer:CREBBP:BNIP3L GeneTP63 TP53I3RABGGTAIGFBP3 TNFRSF10A Gene p-S15,S20,S46-TP53TetramerTNFRSF10C Gene AIFM2 Gene TP53I3 p-S15,S20-TP53 CASP6 (1-293)p-S15,S20-TP53 BIRC5RABGGTB FAS Gene NDRG1CASP2(348-452)NLRC4 Gene BCL2L14PIDD1 Gene p-S15,S20-TP53Tetramer:TRIAP1GeneTP63 PIDD1p-S15,S20-TP53 STEAP3CASP1 Gene (p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):FAS GeneTRAIL signalingTP73 NDRG1 Genep-S1981,Ac-K3016-ATMTP63 PIDD1 GeneBBC3p-S15,S20-TP53Tetramer:CASP6 GeneBNIP3LCASP10 GeneNDRG1 Gene TP63 IGFBP3 Gene TRIAP1TNFRSF10A TRIAP1 CRADDTP53BP2 TP53BP2 TNFRSF10B RGGTp-S15,S20-TP53Tetramer:TP53INP1GeneTNFRSF10A Gene p-S15,S20-TP53 CASP10(1-521)CASP1 Genep-S15,S20-TP53 BID(1-195)CHM PIDDosomeTP53BP2 p-S15,S20-TP53 753326645019, 39, 47, 7427, 38, 45, 80, 84...2, 72, 91956628177824, 90135589766844, 99711003, 58, 60, 97883285986, 23, 3134162661048710257, 7346, 81, 10237, 52, 6540, 484225, 6721, 41


Description

The tumor suppressor TP53 (p53) exerts its tumor suppressive role in part by regulating transcription of a number of genes involved in cell death, mainly apoptotic cell death. The majority of apoptotic genes that are transcriptional targets of TP53 promote apoptosis, but there are also several TP53 target genes that inhibit apoptosis, providing cells with an opportunity to attempt to repair the damage and/or recover from stress.
Pro-apoptotic transcriptional targets of TP53 involve TRAIL death receptors TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2), as well as the FASL/CD95L death receptor FAS (CD95). TRAIL receptors and FAS induce pro-apoptotic signaling in response to external stimuli via extrinsic apoptosis pathway (Wu et al. 1997, Takimoto et al. 2000, Guan et al. 2001, Liu et al. 2004, Ruiz de Almodovar et al. 2004, Liu et al. 2005, Schilling et al. 2009, Wilson et al. 2013). IGFBP3 is a transcriptional target of TP53 that may serve as a ligand for a novel death receptor TMEM219 (Buckbinder et al. 1995, Ingermann et al. 2010).

TP53 regulates expression of a number of genes involved in the intrinsic apoptosis pathway, triggered by the cellular stress. Some of TP53 targets, such as BAX, BID, PMAIP1 (NOXA), BBC3 (PUMA) and probably BNIP3L, AIFM2, STEAP3, TRIAP1 and TP53AIP1, regulate the permeability of the mitochondrial membrane and/or cytochrome C release (Miyashita and Reed 1995, Oda et al. 2000, Samuels-Lev et al. 2001, Nakano and Vousden 2001, Sax et al. 2002, Passer et al. 2003, Bergamaschi et al. 2004, Li et al. 2004, Fei et al. 2004, Wu et al. 2004, Park and Nakamura 2005, Patel et al. 2008, Wang et al. 2012, Wilson et al. 2013). Other pro-apoptotic genes, either involved in the intrinsic apoptosis pathway, extrinsic apoptosis pathway or pyroptosis (inflammation-related cell death), which are transcriptionally regulated by TP53 are cytosolic caspase activators, such as APAF1, PIDD1, and NLRC4, and caspases themselves, such as CASP1, CASP6 and CASP10 (Lin et al. 2000, Robles et al. 2001, Gupta et al. 2001, MacLachlan and El-Deiry 2002, Rikhof et al. 2003, Sadasivam et al. 2005, Brough and Rothwell 2007).<p>It is uncertain how exactly some of the pro-apoptotic TP53 targets, such as TP53I3 (PIG3), RABGGTA, BCL2L14, BCL6, NDRG1 and PERP contribute to apoptosis (Attardi et al. 2000, Guo et al. 2001, Samuels-Lev et al. 2001, Contente et al. 2002, Ihrie et al. 2003, Bergamaschi et al. 2004, Stein et al. 2004, Phan and Dalla-Favera 2004, Jen and Cheung 2005, Margalit et al. 2006, Zhang et al. 2007, Saito et al. 2009, Davies et al. 2009, Giam et al. 2012).<p>TP53 is stabilized in response to cellular stress by phosphorylation on at least serine residues S15 and S20. Since TP53 stabilization precedes the activation of cell death genes, the TP53 tetramer phosphorylated at S15 and S20 is shown as a regulator of pro-apoptotic/pro-cell death genes. Some pro-apoptotic TP53 target genes, such as TP53AIP1, require additional phosphorylation of TP53 at serine residue S46 (Oda et al. 2000, Taira et al. 2007). Phosphorylation of TP53 at S46 is regulated by another TP53 pro-apoptotic target, TP53INP1 (Okamura et al. 2001, Tomasini et al. 2003). Additional post-translational modifications of TP53 may be involved in transcriptional regulation of genes presented in this pathway and this information will be included as evidence becomes available.<p>Activation of some pro-apoptotic TP53 targets, such as BAX, FAS, BBC3 (PUMA) and TP53I3 (PIG3) requires the presence of the complex of TP53 and an ASPP protein, either PPP1R13B (ASPP1) or TP53BP2 (ASPP2) (Samuels-Lev et al. 2001, Bergamaschi et al. 2004, Patel et al. 2008, Wilson et al. 2013), indicating how the interaction with specific co-factors modulates the cellular response/outcome.<p>TP53 family members TP63 and or TP73 can also activate some of the pro-apoptotic TP53 targets, such as FAS, BAX, BBC3 (PUMA), TP53I3 (PIG3), CASP1 and PERP (Bergamaschi et al. 2004, Jain et al. 2005, Ihrie et al. 2005, Patel et al. 2008, Schilling et al. 2009, Celardo et al. 2013).<p>
For a review of the role of TP53 in apoptosis and pro-apoptotic transcriptional targets of TP53, please refer to Riley et al. 2008, Murray-Zmijewski et al. 2008, Bieging et al. 2014, Kruiswijk et al. 2015. View original pathway at:Reactome.</div>

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  81. Seabra MC, Goldstein JL, Südhof TC, Brown MS.; ''Rab geranylgeranyl transferase. A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-Cys.''; PubMed Europe PMC Scholia
  82. Oppermann U.; ''Carbonyl reductases: the complex relationships of mammalian carbonyl- and quinone-reducing enzymes and their role in physiology.''; PubMed Europe PMC Scholia
  83. Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson RS, Wang M, Liang P.; ''NDRG1 is necessary for p53-dependent apoptosis.''; PubMed Europe PMC Scholia
  84. Sprick MR, Rieser E, Stahl H, Grosse-Wilde A, Weigand MA, Walczak H.; ''Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8.''; PubMed Europe PMC Scholia
  85. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P.; ''Toxic proteins released from mitochondria in cell death.''; PubMed Europe PMC Scholia
  86. Poyet JL, Srinivasula SM, Tnani M, Razmara M, Fernandes-Alnemri T, Alnemri ES.; ''Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1.''; PubMed Europe PMC Scholia
  87. Li Y, Zhao Y, Hu J, Xiao J, Qu L, Wang Z, Ma D, Chen Y.; ''A novel ER-localized transmembrane protein, EMC6, interacts with RAB5A and regulates cell autophagy.''; PubMed Europe PMC Scholia
  88. Margalit O, Amram H, Amariglio N, Simon AJ, Shaklai S, Granot G, Minsky N, Shimoni A, Harmelin A, Givol D, Shohat M, Oren M, Rechavi G.; ''BCL6 is regulated by p53 through a response element frequently disrupted in B-cell non-Hodgkin lymphoma.''; PubMed Europe PMC Scholia
  89. Marzec KA, Lin MZ, Martin JL, Baxter RC.; ''Involvement of p53 in insulin-like growth factor binding protein-3 regulation in the breast cancer cell response to DNA damage.''; PubMed Europe PMC Scholia
  90. Wang S, El-Deiry WS.; ''TRAIL and apoptosis induction by TNF-family death receptors.''; PubMed Europe PMC Scholia
  91. Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA.; ''Molecular cloning of the interleukin-1 beta converting enzyme.''; PubMed Europe PMC Scholia
  92. Passer BJ, Nancy-Portebois V, Amzallag N, Prieur S, Cans C, Roborel de Climens A, Fiucci G, Bouvard V, Tuynder M, Susini L, Morchoisne S, Crible V, Lespagnol A, Dausset J, Oren M, Amson R, Telerman A.; ''The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase.''; PubMed Europe PMC Scholia
  93. Ihrie RA, Marques MR, Nguyen BT, Horner JS, Papazoglu C, Bronson RT, Mills AA, Attardi LD.; ''Perp is a p63-regulated gene essential for epithelial integrity.''; PubMed Europe PMC Scholia
  94. Meek DW, Anderson CW.; ''Posttranslational modification of p53: cooperative integrators of function.''; PubMed Europe PMC Scholia
  95. Baron RA, Seabra MC.; ''Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate.''; PubMed Europe PMC Scholia
  96. Lin Y, Ma W, Benchimol S.; ''Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis.''; PubMed Europe PMC Scholia
  97. Zhang AH, Rao JN, Zou T, Liu L, Marasa BS, Xiao L, Chen J, Turner DJ, Wang JY.; ''p53-dependent NDRG1 expression induces inhibition of intestinal epithelial cell proliferation but not apoptosis after polyamine depletion.''; PubMed Europe PMC Scholia
  98. Guo B, Godzik A, Reed JC.; ''Bcl-G, a novel pro-apoptotic member of the Bcl-2 family.''; PubMed Europe PMC Scholia
  99. Wang J, Chun HJ, Wong W, Spencer DM, Lenardo MJ.; ''Caspase-10 is an initiator caspase in death receptor signaling.''; PubMed Europe PMC Scholia
  100. Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y, Taya Y.; ''p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53.''; PubMed Europe PMC Scholia
  101. Schilling T, Schleithoff ES, Kairat A, Melino G, Stremmel W, Oren M, Krammer PH, Müller M.; ''Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 family.''; PubMed Europe PMC Scholia
  102. Lackner MR, Kindt RM, Carroll PM, Brown K, Cancilla MR, Chen C, de Silva H, Franke Y, Guan B, Heuer T, Hung T, Keegan K, Lee JM, Manne V, O'Brien C, Parry D, Perez-Villar JJ, Reddy RK, Xiao H, Zhan H, Cockett M, Plowman G, Fitzgerald K, Costa M, Ross-Macdonald P.; ''Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors.''; PubMed Europe PMC Scholia
  103. MacLachlan TK, El-Deiry WS.; ''Apoptotic threshold is lowered by p53 transactivation of caspase-6.''; PubMed Europe PMC Scholia
  104. Hengartner MO.; ''The biochemistry of apoptosis.''; PubMed Europe PMC Scholia
  105. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N.; ''Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
115032view16:57, 25 January 2021ReactomeTeamReactome version 75
113476view11:55, 2 November 2020ReactomeTeamReactome version 74
112675view16:06, 9 October 2020ReactomeTeamReactome version 73
101592view11:46, 1 November 2018ReactomeTeamreactome version 66
101128view21:31, 31 October 2018ReactomeTeamreactome version 65
100656view20:05, 31 October 2018ReactomeTeamreactome version 64
100206view16:50, 31 October 2018ReactomeTeamreactome version 63
99757view15:16, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99319view12:47, 31 October 2018ReactomeTeamreactome version 62
93790view13:36, 16 August 2017ReactomeTeamreactome version 61
93324view11:20, 9 August 2017ReactomeTeamreactome version 61
88393view15:16, 4 August 2016FehrhartOntology Term : 'cell death pathway' added !
88392view15:15, 4 August 2016FehrhartOntology Term : 'regulatory pathway' added !
86411view09:17, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(p-S15,S20-TP53,TP63):PERP GeneComplexR-HSA-6800835 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):BAX GeneComplexR-HSA-3700978 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):BBC3 GeneComplexR-HSA-4331345 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):FAS GeneComplexR-HSA-6799810 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):TP53I3 GeneComplexR-HSA-6799461 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2)ComplexR-HSA-6799788 (Reactome)
(p-S15,S20-TP53,TP63,TP73):CASP1 GeneComplexR-HSA-6798078 (Reactome)
1,2-NaphthoquinoneMetaboliteCHEBI:34055 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
AIFM2 Gene ProteinENSG00000042286 (Ensembl)
AIFM2 GeneGeneProductENSG00000042286 (Ensembl)
AIFM2ProteinQ9BRQ8 (Uniprot-TrEMBL)
APAF1 Gene ProteinENSG00000120868 (Ensembl)
APAF1 GeneGeneProductENSG00000120868 (Ensembl)
APAF1ProteinO14727 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
Apoptotic execution phasePathwayR-HSA-75153 (Reactome) In the execution phase of apoptosis, effector caspases cleave vital cellular proteins leading to the morphological changes that characterize apoptosis. These changes include destruction of the nucleus and other organelles, DNA fragmentation, chromatin condensation, cell shrinkage and cell detachment and membrane blebbing (reviewed in Fischer et al., 2003).
BAX Gene ProteinENSG00000087088 (Ensembl)
BAX GeneGeneProductENSG00000087088 (Ensembl)
BAXProteinQ07812 (Uniprot-TrEMBL)
BBC3 Gene ProteinENSG00000105327 (Ensembl)
BBC3 GeneGeneProductENSG00000105327 (Ensembl)
BBC3ProteinQ9BXH1 (Uniprot-TrEMBL)
BCL2L14 Gene ProteinENSG00000121380 (Ensembl)
BCL2L14 GeneGeneProductENSG00000121380 (Ensembl)
BCL2L14ProteinQ9BZR8 (Uniprot-TrEMBL)
BCL6 Gene ProteinENSG00000113916 (Ensembl)
BCL6 GeneGeneProductENSG00000113916 (Ensembl)
BCL6ProteinP41182 (Uniprot-TrEMBL)
BID Gene ProteinENSG00000015475 (Ensembl)
BID GeneGeneProductENSG00000015475 (Ensembl)
BID(1-195)ProteinP55957 (Uniprot-TrEMBL)
BIRC5 Gene ProteinENSG00000089685 (Ensembl)
BIRC5 GeneGeneProductENSG00000089685 (Ensembl)
BIRC5ProteinO15392 (Uniprot-TrEMBL)
BNIP3L Gene ProteinENSG00000104765 (Ensembl)
BNIP3L GeneGeneProductENSG00000104765 (Ensembl)
BNIP3L ProteinO60238 (Uniprot-TrEMBL)
BNIP3LProteinO60238 (Uniprot-TrEMBL)
CASP1 Gene ProteinENSG00000137752 (Ensembl)
CASP1 GeneGeneProductENSG00000137752 (Ensembl)
CASP1(1-404)ProteinP29466 (Uniprot-TrEMBL)
CASP10 Gene ProteinENSG00000003400 (Ensembl)
CASP10 GeneGeneProductENSG00000003400 (Ensembl)
CASP10(1-521)ProteinQ92851 (Uniprot-TrEMBL)
CASP2(170-325)ProteinP42575 (Uniprot-TrEMBL)
CASP2(2-452) ProteinP42575 (Uniprot-TrEMBL)
CASP2(2-452)ProteinP42575 (Uniprot-TrEMBL)
CASP2(348-452)ProteinP42575 (Uniprot-TrEMBL)
CASP6 (1-293)ProteinP55212 (Uniprot-TrEMBL)
CASP6 Gene ProteinENSG00000138794 (Ensembl)
CASP6 GeneGeneProductENSG00000138794 (Ensembl)
CHM ProteinP24386 (Uniprot-TrEMBL)
CHMProteinP24386 (Uniprot-TrEMBL)
CRADD ProteinP78560 (Uniprot-TrEMBL)
CRADDProteinP78560 (Uniprot-TrEMBL)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CREBBPProteinQ92793 (Uniprot-TrEMBL)
FAS Gene ProteinENSG00000026103 (Ensembl)
FAS GeneGeneProductENSG00000026103 (Ensembl)
FASProteinP25445 (Uniprot-TrEMBL)
FasL/ CD95L signalingPathwayR-HSA-75157 (Reactome) The Fas family of cell surface receptors initiate the apototic pathway through interaction with the external ligand, FasL. The cytoplasmic domain of Fas interacts with a number of molecules in the transduction of the external signal to the cytoplasmic side of the cell membrane. The most notable cytoplasmic domain is the Death Domain (DD) that is involved in recruiting the FAS-associating death domain-containing protein (FADD). This interaction drives downstream events.
H+MetaboliteCHEBI:15378 (ChEBI)
IGFBP3 Gene ProteinENSG00000146674 (Ensembl)
IGFBP3 GeneGeneProductENSG00000146674 (Ensembl)
IGFBP3 ProteinP17936 (Uniprot-TrEMBL)
IGFBP3:TMEM219ComplexR-HSA-6800024 (Reactome)
IGFBP3ProteinP17936 (Uniprot-TrEMBL)
Innate Immune SystemPathwayR-HSA-168249 (Reactome) Innate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Interleukin-1 processingPathwayR-HSA-448706 (Reactome) The IL-1 family of cytokines that interact with the Type 1 IL-1R include IL-1 Alpha (IL1A), IL-1 Beta (IL1B) and the IL-1 receptor antagonist protein (IL1RAP). IL1RAP is synthesized with a signal peptide and secreted as a mature protein via the classical secretory pathway. IL1A and IL1B are synthesised as cytoplasmic precursors (pro-IL1A and pro-IL1B) in activated cells. They have no signal sequence, precluding secretion via the classical ER-Golgi route (Rubartelli et al. 1990). Processing of pro-IL1B to the active form requires caspase-1 (Thornberry et al. 1992), which is itself activated by a molecular scaffold termed the inflammasome (Martinon et al. 2002). Processing and release of IL1B are thought to be closely linked, because mature IL1B is only seen inside inflammatory cells just prior to release (Brough et al. 2003). It has been reported that in monocytes a fraction of cellular IL1B is released by the regulated secretion of late endosomes and early lysosomes, and that this may represent a cellular compartment where caspase-1 processing of pro-IL1B takes place (Andrei et al. 1999). Shedding of microvesicles from the plasma membrane has also been proposed as a mechanism of secretion (MacKenzie et al. 2001). These proposals superceded previous models in which non-specific release due to cell lysis and passage through a plasma membrane pore were considered. However, there is evidence in the literature that supports all of these mechanisms and there is still controversy over how IL1B exits from cells (Brough & Rothwell 2007). A calpain-like potease has been reported to be important for the processing of pro-IL1A, but much less is known about how IL1A is released from cells and what specific roles it plays in biology.
Intrinsic Pathway for ApoptosisPathwayR-HSA-109606 (Reactome) The intrinsic (Bcl-2 inhibitable or mitochondrial) pathway of apoptosis functions in response to various types of intracellular stress including growth factor withdrawal, DNA damage, unfolding stresses in the endoplasmic reticulum and death receptor stimulation. Following the reception of stress signals, proapoptotic BCL-2 family proteins are activated and subsequently interact with and inactivate antiapoptotic BCL-2 proteins. This interaction leads to the destabilization of the mitochondrial membrane and release of apoptotic factors. These factors induce the caspase proteolytic cascade, chromatin condensation, and DNA fragmentation, ultimately leading to cell death. The key players in the Intrinsic pathway are the Bcl-2 family of proteins that are critical death regulators residing immediately upstream of mitochondria. The Bcl-2 family consists of both anti- and proapoptotic members that possess conserved alpha-helices with sequence conservation clustered in BCL-2 Homology (BH) domains. Proapoptotic members are organized as follows:

1. "Multidomain" BAX family proteins such as BAX, BAK etc. that display sequence conservation in their BH1-3 regions. These proteins act downstream in mitochondrial disruption.

2. "BH3-only" proteins such as BID,BAD, NOXA, PUMA,BIM, and BMF have only the short BH3 motif. These act upstream in the pathway, detecting developmental death cues or intracellular damage. Anti-apoptotic members like Bcl-2, Bcl-XL and their relatives exhibit homology in all segments BH1-4. One of the critical functions of BCL-2/BCL-XL proteins is to maintain the integrity of the mitochondrial outer membrane.

Iron uptake and transportPathwayR-HSA-917937 (Reactome) The transport of iron between cells is mediated by transferrin. However, iron can also enter and leave cells not only by itself, but also in the form of heme and siderophores. When entering the cell via the main path (by transferrin endocytosis), its goal is not the (still elusive) chelated iron pool in the cytosol nor the lysosomes but the mitochondria, where heme is synthesized and iron-sulfur clusters are assembled (Kurz et al,2008, Hower et al 2009, Richardson et al 2010).
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
NDRG1 Gene ProteinENSG00000104419 (Ensembl)
NDRG1 GeneGeneProductENSG00000104419 (Ensembl)
NDRG1ProteinQ92597 (Uniprot-TrEMBL)
NLRC4 Gene ProteinENSG00000091106 (Ensembl)
NLRC4 GeneGeneProductENSG00000091106 (Ensembl)
NLRC4ProteinQ9NPP4 (Uniprot-TrEMBL)
O2.-MetaboliteCHEBI:18421 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
PAMetaboliteCHEBI:16337 (ChEBI)
PERP Gene ProteinENSG00000112378 (Ensembl)
PERP GeneGeneProductENSG00000112378 (Ensembl)
PERPProteinQ96FX8 (Uniprot-TrEMBL)
PIDD1 Gene ProteinENSG00000177595 (Ensembl)
PIDD1 GeneGeneProductENSG00000177595 (Ensembl)
PIDD1ProteinQ9HB75 (Uniprot-TrEMBL)
PIDDosome:CASP2(2-452)ComplexR-HSA-6800803 (Reactome)
PIDDosomeComplexR-HSA-6800782 (Reactome)
PMAIP1 Gene ProteinENSG00000141682 (Ensembl)
PMAIP1 GeneGeneProductENSG00000141682 (Ensembl)
PMAIP1ProteinQ13794 (Uniprot-TrEMBL)
PPP1R13B ProteinQ96KQ4 (Uniprot-TrEMBL)
PRELID1 ProteinQ9Y255 (Uniprot-TrEMBL)
PRELID1ProteinQ9Y255 (Uniprot-TrEMBL)
RABGGTA Gene ProteinENSG00000100949 (Ensembl)
RABGGTA GeneGeneProductENSG00000100949 (Ensembl)
RABGGTA ProteinQ92696 (Uniprot-TrEMBL)
RABGGTAProteinQ92696 (Uniprot-TrEMBL)
RABGGTB ProteinP53611 (Uniprot-TrEMBL)
RABGGTBProteinP53611 (Uniprot-TrEMBL)
RGGT:CHMComplexR-HSA-6801111 (Reactome)
RGGTComplexR-HSA-6801105 (Reactome)
Regulation of

Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding

Proteins (IGFBPs)
PathwayR-HSA-381426 (Reactome) The family of Insulin like Growth Factor Binding Proteins (IGFBPs) share 50% amino acid identity with conserved N terminal and C terminal regions responsible for binding Insulin like Growth Factors I and II (IGF I and IGF II). Most circulating IGFs are in complexes with IGFBPs, which are believed to increase the residence of IGFs in the body, modulate availability of IGFs to target receptors for IGFs, reduce insulin like effects of IGFs, and act as signaling molecules independently of IGFs.

About 75% of circulating IGFs are in 1500 220 KDa complexes with IGFBP3 and ALS. Such complexes are too large to pass the endothelial barrier. The remaining 20 25% of IGFs are bound to other IGFBPs in 40 50 KDa complexes. IGFs are released from IGF:IGFBP complexes by proteolysis of the IGFBP. IGFs become active after release, however IGFs may also have activity when still bound to some IGFBPs. IGFBP1 is enriched in amniotic fluid and is produced in the liver under control of insulin (insulin suppresses production). IGFBP1 binding stimulates IGF function. It is unknown which if any protease degrades IGFBP1. IGFBP2 is enriched in cerebrospinal fluid; its binding inhibits IGF function. IGFBP2 is not significantly degraded in circulation. IGFB3, which binds most IGF in the body is enriched in follicular fluid and found in many other tissues. IGFBP 3 may be cleaved by plasmin, thrombin, Prostate specific Antigen (PSA, KLK3), Matrix Metalloprotease-1 (MMP1), and Matrix Metalloprotease-2 (MMP2). IGFBP3 also binds extracellular matrix and binding lowers its affinity for IGFs. IGFBP3 binding stimulates the effects of IGFs. IGFBP4 acts to inhibit IGF function and is cleaved by Pregnancy associated Plasma Protein A (PAPPA) to release IGF. IGFBP5 is enriched in bone matrix; its binding stimulates IGF function. IGFBP5 is cleaved by Pregnancy Associated Plasma Protein A2 (PAPPA2), ADAM9, complement C1s from smooth muscle, and thrombin. Only the cleavage site for PAPPA2 is known. IGFBP6 is enriched in cerebrospinal fluid. It is unknown which if any protease degrades IGFBP6.

Regulation of TP53 ActivityPathwayR-HSA-5633007 (Reactome) Protein stability and transcriptional activity of TP53 (p53) tumor suppressor are regulated by post-translational modifications that include ubiquitination, phosphorylation, acetylation, methylation, sumoylation and prolyl-isomerization (Kruse and Gu 2009, Meek and Anderson 2009, Santiago et al. 2013, Mantovani et al. 2015). In addition to post-translational modifications, the activity of TP53 is also regulated by binding of transcription co-factors.

In unstressed cells, TP53 protein levels are low due to MDM2-mediated ubiquitination of TP53, which triggers proteasome-mediated degradation. In response to stress, TP53 undergoes stabilizing phosphorylation, mainly at serine residues S15 and S20. Several different kinases can phosphorylate TP53 at these sites, but the main S15 kinases are considered to be ATM and ATR, while the main S20 kinases are considered to be CHEK2 and CHEK1. Additional phosphorylation of TP53 at serine residue S46 promotes transcription of pro-apoptotic, rather than cell cycle arrest genes.

Acetylation mainly has a positive impact on transcriptional activity of TP53, while methylation can both positively and negatively regulate TP53.

Some posttranslational modifications regulate interaction of TP53 with transcriptional co-factors, some of which are themselves transcriptional targets of TP53.

For review of the complex network of TP53 regulation, please refer to Kruse and Gu 2009, and Meek and Anderson 2009.

STEAP3 Gene ProteinENSG00000115107 (Ensembl)
STEAP3 GeneGeneProductENSG00000115107 (Ensembl)
STEAP3 ProteinQ658P3 (Uniprot-TrEMBL)
STEAP3:BNIP3LComplexR-HSA-6801198 (Reactome)
STEAP3ProteinQ658P3 (Uniprot-TrEMBL)
TMEM219 ProteinQ86XT9 (Uniprot-TrEMBL)
TMEM219ProteinQ86XT9 (Uniprot-TrEMBL)
TNFRSF10A Gene ProteinENSG00000104689 (Ensembl)
TNFRSF10A ProteinO00220 (Uniprot-TrEMBL)
TNFRSF10A,

TNFRSF10B, TNFRSF10C,

TNFRSF10D
ComplexR-HSA-6801323 (Reactome)
TNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10D GenesComplexR-HSA-5633424 (Reactome)
TNFRSF10B Gene ProteinENSG00000120889 (Ensembl)
TNFRSF10B ProteinO14763 (Uniprot-TrEMBL)
TNFRSF10C Gene ProteinENSG00000173535 (Ensembl)
TNFRSF10C ProteinO14798 (Uniprot-TrEMBL)
TNFRSF10D Gene ProteinENSG00000173530 (Ensembl)
TNFRSF10D ProteinQ9UBN6 (Uniprot-TrEMBL)
TP53AIP1 Gene ProteinENSG00000120471 (Ensembl)
TP53AIP1 GeneGeneProductENSG00000120471 (Ensembl)
TP53AIP1ProteinQ9HCN2 (Uniprot-TrEMBL)
TP53BP2 ProteinQ13625 (Uniprot-TrEMBL)
TP53I3 DimerComplexR-HSA-6799448 (Reactome)
TP53I3 Gene ProteinENSG00000115129 (Ensembl)
TP53I3 GeneGeneProductENSG00000115129 (Ensembl)
TP53I3 ProteinQ53FA7 (Uniprot-TrEMBL)
TP53I3ProteinQ53FA7 (Uniprot-TrEMBL)
TP53INP1 Gene ProteinENSG00000164938 (Ensembl)
TP53INP1 GeneGeneProductENSG00000164938 (Ensembl)
TP53INP1ProteinQ96A56 (Uniprot-TrEMBL)
TP63 ProteinQ9H3D4 (Uniprot-TrEMBL)
TP73 ProteinO15350 (Uniprot-TrEMBL)
TRAIL signalingPathwayR-HSA-75158 (Reactome) Tumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family. This group of apoptosis induction pathways all work through protein interactions mediated by the intracellular death domain (DD), encoded within the cytoplasmic domain of the receptor. TRAIL selectively induces apoptosis through its interaction with the Fas-associated death domain protein (FADD) and caspase-8/10 (Wang S & el-Deiry WS 2003; Sprick MR et al. 2002). TRAIL and its receptors, TRAIL-R1 and TRAIL-R2, were shown to be rapidly endocytosed via clathrin-dependent and -independent manner in human Burkitt's lymphoma B cells (BJAB) (Kohlhaas SL et al. 2007). However, FADD and caspase-8 were able to bind TRAIL-R1/R2 in TRAIL-stimulated BJAB cells at 4oC (at which membrane trafficking is inhibited), suggesting that the endocytosis was not required for an assembly of the functional TRAIL DISC complex. Moreover, blocking of clathrin-dependent endocytosis did not interfere with the capacity of TRAIL to promote apoptosis (Kohlhaas SL et al. 2007).
TRIAP1 Gene ProteinENSG00000170855 (Ensembl)
TRIAP1 GeneGeneProductENSG00000170855 (Ensembl)
TRIAP1 ProteinO43715 (Uniprot-TrEMBL)
TRIAP1:PRELID1ComplexR-HSA-6801235 (Reactome)
TRIAP1ProteinO43715 (Uniprot-TrEMBL)
ZNF420 ProteinQ8TAQ5 (Uniprot-TrEMBL)
ZNF420:TP53AIP1 GeneComplexR-HSA-6798631 (Reactome)
ZNF420ProteinQ8TAQ5 (Uniprot-TrEMBL)
p-S15,S20,S46-TP53

Tetramer:TP53AIP1

Gene
ComplexR-HSA-6798606 (Reactome)
p-S15,S20,S46-TP53 TetramerComplexR-HSA-6798371 (Reactome)
p-S15,S20,S46-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15,S20-TP53 Tetramer:AIFM2 GeneComplexR-HSA-6791298 (Reactome)
p-S15,S20-TP53 Tetramer:APAF1 GeneComplexR-HSA-6791350 (Reactome)
p-S15,S20-TP53

Tetramer:BCL2L14

Gene
ComplexR-HSA-6791328 (Reactome)
p-S15,S20-TP53 Tetramer:BCL6 GeneComplexR-HSA-6800252 (Reactome)
p-S15,S20-TP53 Tetramer:BID GeneComplexR-HSA-6791290 (Reactome)
p-S15,S20-TP53 Tetramer:BIRC5 GeneComplexR-HSA-6797767 (Reactome)
p-S15,S20-TP53

Tetramer:CASP10

Gene
ComplexR-HSA-6798147 (Reactome)
p-S15,S20-TP53 Tetramer:CASP6 GeneComplexR-HSA-6798123 (Reactome)
p-S15,S20-TP53 Tetramer:CREBBP:BNIP3L GeneComplexR-HSA-6797994 (Reactome)
p-S15,S20-TP53

Tetramer:IGFBP3

Gene
ComplexR-HSA-6800034 (Reactome)
p-S15,S20-TP53 Tetramer:NDRG1 GeneComplexR-HSA-5633301 (Reactome)
p-S15,S20-TP53 Tetramer:PIDD1 GeneComplexR-HSA-6800276 (Reactome)
p-S15,S20-TP53

Tetramer:PMAIP1

Gene
ComplexR-HSA-4331332 (Reactome)
p-S15,S20-TP53

Tetramer:RABGGTA

Gene
ComplexR-HSA-6801088 (Reactome)
p-S15,S20-TP53

Tetramer:STEAP3

Gene
ComplexR-HSA-6801165 (Reactome)
p-S15,S20-TP53 Tetramer:TNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10D GenesComplexR-HSA-5633436 (Reactome)
p-S15,S20-TP53

Tetramer:TP53INP1

Gene
ComplexR-HSA-6799421 (Reactome)
p-S15,S20-TP53

Tetramer:TRIAP1

Gene
ComplexR-HSA-6801208 (Reactome)
p-S15,S20-TP53 TetramerComplexR-HSA-3222171 (Reactome)
p-S15,S20-TP53 ProteinP04637 (Uniprot-TrEMBL)
p-S15,S20-TP53,TP63,TP73ComplexR-HSA-6798076 (Reactome)
p-S15,S20-TP53,TP63ComplexR-HSA-6800828 (Reactome)
p-S15,S20-TP53:NLRC4 GeneComplexR-HSA-6801357 (Reactome)
p-S1981,Ac-K3016-ATMProteinQ13315 (Uniprot-TrEMBL)
p-S68-ZNF420ProteinQ8TAQ5 (Uniprot-TrEMBL)
p-T788-PIDD1 ProteinQ9HB75 (Uniprot-TrEMBL)
p-T788-PIDD1ProteinQ9HB75 (Uniprot-TrEMBL)
phosphatidic acidMetaboliteCHEBI:16337 (ChEBI)
semiquinoneMetaboliteCHEBI:15817 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
(p-S15,S20-TP53,TP63):PERP GeneArrowR-HSA-6800816 (Reactome)
(p-S15,S20-TP53,TP63):PERP GeneArrowR-HSA-6800836 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):BAX GeneArrowR-HSA-3700981 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):BAX GeneArrowR-HSA-3700984 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):BBC3 GeneArrowR-HSA-139913 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):BBC3 GeneArrowR-HSA-4331340 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):FAS GeneArrowR-HSA-6799815 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):FAS GeneArrowR-HSA-6800001 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):TP53I3 GeneArrowR-HSA-6799441 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2):TP53I3 GeneArrowR-HSA-6799462 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2)R-HSA-3700981 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2)R-HSA-4331340 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2)R-HSA-6799462 (Reactome)
(p-S15,S20-TP53,TP63,TP73):(PPP1R13B,TP53BP2)R-HSA-6799815 (Reactome)
(p-S15,S20-TP53,TP63,TP73):CASP1 GeneArrowR-HSA-6798081 (Reactome)
(p-S15,S20-TP53,TP63,TP73):CASP1 GeneArrowR-HSA-6798082 (Reactome)
1,2-NaphthoquinoneArrowR-HSA-6799733 (Reactome)
1,2-NaphthoquinoneR-HSA-6799722 (Reactome)
ADPArrowR-HSA-6799097 (Reactome)
ADPArrowR-HSA-6800490 (Reactome)
AIFM2 GeneR-HSA-6791302 (Reactome)
AIFM2 GeneR-HSA-6791306 (Reactome)
AIFM2ArrowR-HSA-6791306 (Reactome)
APAF1 GeneR-HSA-6791348 (Reactome)
APAF1 GeneR-HSA-6791349 (Reactome)
APAF1ArrowR-HSA-6791348 (Reactome)
ATPR-HSA-6799097 (Reactome)
ATPR-HSA-6800490 (Reactome)
BAX GeneR-HSA-3700981 (Reactome)
BAX GeneR-HSA-3700984 (Reactome)
BAXArrowR-HSA-3700984 (Reactome)
BBC3 GeneR-HSA-139913 (Reactome)
BBC3 GeneR-HSA-4331340 (Reactome)
BBC3ArrowR-HSA-139913 (Reactome)
BCL2L14 GeneR-HSA-6791323 (Reactome)
BCL2L14 GeneR-HSA-6791327 (Reactome)
BCL2L14ArrowR-HSA-6791323 (Reactome)
BCL6 GeneR-HSA-6800250 (Reactome)
BCL6 GeneR-HSA-6800253 (Reactome)
BCL6ArrowR-HSA-6800250 (Reactome)
BID GeneR-HSA-6791285 (Reactome)
BID GeneR-HSA-6791291 (Reactome)
BID(1-195)ArrowR-HSA-6791291 (Reactome)
BIRC5 GeneR-HSA-6797763 (Reactome)
BIRC5 GeneR-HSA-6797766 (Reactome)
BIRC5ArrowR-HSA-6797763 (Reactome)
BNIP3L GeneR-HSA-6797993 (Reactome)
BNIP3L GeneR-HSA-6798004 (Reactome)
BNIP3LArrowR-HSA-6798004 (Reactome)
BNIP3LR-HSA-6801195 (Reactome)
CASP1 GeneR-HSA-6798081 (Reactome)
CASP1 GeneR-HSA-6798082 (Reactome)
CASP1(1-404)ArrowR-HSA-6798081 (Reactome)
CASP10 GeneR-HSA-6798138 (Reactome)
CASP10 GeneR-HSA-6798139 (Reactome)
CASP10(1-521)ArrowR-HSA-6798139 (Reactome)
CASP2(170-325)ArrowR-HSA-6800797 (Reactome)
CASP2(2-452)R-HSA-6800798 (Reactome)
CASP2(348-452)ArrowR-HSA-6800797 (Reactome)
CASP6 (1-293)ArrowR-HSA-6798126 (Reactome)
CASP6 GeneR-HSA-6798126 (Reactome)
CASP6 GeneR-HSA-6798129 (Reactome)
CHMR-HSA-6801109 (Reactome)
CRADDR-HSA-6800794 (Reactome)
CREBBPR-HSA-6797993 (Reactome)
FAS GeneR-HSA-6799815 (Reactome)
FAS GeneR-HSA-6800001 (Reactome)
FASArrowR-HSA-6800001 (Reactome)
H+R-HSA-6799722 (Reactome)
IGFBP3 GeneR-HSA-6800042 (Reactome)
IGFBP3 GeneR-HSA-6800044 (Reactome)
IGFBP3:TMEM219ArrowR-HSA-6800035 (Reactome)
IGFBP3ArrowR-HSA-6800044 (Reactome)
IGFBP3R-HSA-6800035 (Reactome)
NADP+ArrowR-HSA-6799722 (Reactome)
NADPHR-HSA-6799722 (Reactome)
NDRG1 GeneR-HSA-5633295 (Reactome)
NDRG1 GeneR-HSA-5633314 (Reactome)
NDRG1ArrowR-HSA-5633314 (Reactome)
NLRC4 GeneR-HSA-6801355 (Reactome)
NLRC4 GeneR-HSA-6801415 (Reactome)
NLRC4ArrowR-HSA-6801415 (Reactome)
O2.-ArrowR-HSA-6799733 (Reactome)
O2R-HSA-6799733 (Reactome)
PAR-HSA-6801250 (Reactome)
PERP GeneR-HSA-6800816 (Reactome)
PERP GeneR-HSA-6800836 (Reactome)
PERPArrowR-HSA-6800816 (Reactome)
PIDD1 GeneR-HSA-6800279 (Reactome)
PIDD1 GeneR-HSA-6800396 (Reactome)
PIDD1ArrowR-HSA-6800396 (Reactome)
PIDD1R-HSA-6800490 (Reactome)
PIDDosome:CASP2(2-452)ArrowR-HSA-6800798 (Reactome)
PIDDosome:CASP2(2-452)R-HSA-6800797 (Reactome)
PIDDosome:CASP2(2-452)mim-catalysisR-HSA-6800797 (Reactome)
PIDDosomeArrowR-HSA-6800794 (Reactome)
PIDDosomeArrowR-HSA-6800797 (Reactome)
PIDDosomeR-HSA-6800798 (Reactome)
PMAIP1 GeneR-HSA-140214 (Reactome)
PMAIP1 GeneR-HSA-4331331 (Reactome)
PMAIP1ArrowR-HSA-140214 (Reactome)
PRELID1R-HSA-6801242 (Reactome)
R-HSA-139913 (Reactome) TP53 (p53) stimulates the transcription of BBC3 (PUMA) (p53 upregulated modulator of apoptosis) (Nakano and Vousden 2001). The transcription of BBC3 is also stimulated by p53 family members TP63 (p63) and TP73 (p73) (Bergamaschi et al. 2004, Patel et al. 2008). ASPP proteins PPP1R13B (ASPP1) and TP53BP2 (ASPP2) form a complex with p53 family members and enhance transcriptional activation of BBC3 (Bergamaschi et al. 2004, Patel et al. 2008, Wilson et al. 2013).
R-HSA-140214 (Reactome) TP53 (p53) stimulates transcription of PMAIP1 (NOXA) (Oda et al. 2000, Li et al. 2004). The complex of TP53 with ASPP proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) is likely involved in the transcriptional activation of PMAIP1 (Wang et al. 2012, Wilson et al. 2013).
R-HSA-3700981 (Reactome) TP53 (p53) binds the p53 response element in the promoter of the BAX gene (Miyashita and Reed 1995). TP53 family members TP63 (p63) and TP73 (p73) can also bind the BAX promoter. Complex formation between ASPP proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) and p53 family members TP53 (Samuels-Lev et al. 2001), TP63 or TP73 (Bergamaschi et al. 2004) enhances binding of p53 family members to the BAX promoter.
R-HSA-3700984 (Reactome) BAX is a member of the group of pro-apoptotic proteins possessing the BH3 domain. These proteins undergo conformational activation leading to oligomerization and insertion in the outer mitochondrial membrane. This process is presumed to result in permeabilization of outer mitochondrial membrane and egress of apoptogenic factors, such as cytochrome C, that activate the caspase cascade leading to cellular demise. BAX gene transcription is stimulated by binding of TP53 (p53) (Miyashita and Reed 1995) or p53 family members TP63 (p63) and TP73 (p73) (Bergamaschi et al. 2004) to the p53 response element in the BAX gene promoter. ASSP proteins PPP1R13B (ASPP1) and TP53BP2 (ASPP2) form a complex with p53 family members and enhance transcription of the BAX gene (Samuels-Lev et al. 2001, Bergamaschi et al. 2004).
R-HSA-4331331 (Reactome) TP53 (p53) binds the promoter of the PMAIP1 (NOXA) gene to induce PMAIP1 transcription (Oda et al. 2000, Li et al. 2004). TP53 likely associates with the PMAIP1 promoter as part of the complex with ASPP proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) (Wang et al. 2012, Wilson et al. 2013).
R-HSA-4331340 (Reactome) TP53 (p53) binding sites are found in the promoter (Han et al. 2001) and intron 1 (Nakano and Vousden 2001) of the BBC3 (PUMA) gene, and are necessary for TP53-mediated induction of BBC3 transcription. TP53 family members TP63 (p63) and TP73 (p73) can also bind p53 response elements within the BBC3 gene locus (Bergamaschi et al. 2004, Patel et al. 2008). Formation of the complex between TP53 family members and ASPP proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) enhances binding of the p53 family members to the BBC3 gene locus (Bergamaschi et al. 2004, Patel et al. 2008, Wilson et al. 2013).
R-HSA-5633295 (Reactome) TP53 (p53) binds p53-response element(s) in the promoter of the NDRG1 gene (Stein et al. 2004, Zhang et al. 2007).
R-HSA-5633314 (Reactome) Binding of TP53 (p53) to the NDRG1 gene promoter stimulates NDRG1 expression (Stein et al. 2004, Zhang et al. 2007). NDRG1 may positively regulate TP53-mediated apoptosis (Stein et al. 2004) or TP53-mediated cell cycle arrest (Zhang et al. 2007). The exact function of NDRG1 has not been elucidated. Most studies suggest that NDRG1 has a tumor suppressive role, but there are conflicting reports, showing that NDRG1 may act as an oncogene in some settings (reviewed by Liu et al. 2012, Sun and Cao 2013).
R-HSA-5633414 (Reactome) TP53 (p53) binds p53-binding sites located in the first introns of the TNFRSF10A (DR4) (Liu et al. 2004), TNFRSF10B (DR5) (Takimoto et al. 2000), TNFRSF10C (DCR1) (Ruiz de Almodovar et al. 2004) and TNFRSF10D (DCR2) (Liu et al. 2005) genes.
R-HSA-5633441 (Reactome) TP53 (p53) directly stimulates transcription of genes encoding TRAIL (TNF-related apoptosis-inducing ligand) receptors, also known as death receptors, TNFRSF10A (DR4) (Guan et al. 2001, Liu et al. 2004), TNFRSF10B (DR5) (Wu et al. 1997, Takimoto et al. 2000), TNFRSF10C (DCR1) (Ruiz de Almodovar et al. 2004) and TNFRSF10D (DCR2) (Liu et al. 2005). These receptors are involved in TRAIL signaling, which constitutes a part of the extrinsic apoptotis pathway.
R-HSA-6791285 (Reactome) TP53 (p53) binds evolutionarily conserved p53 response elements in the promoter of the BID gene (Sax et al. 2002).
R-HSA-6791291 (Reactome) TP53 (p53) directly stimulates BID gene transcription by binding to p53 response elements in the BID gene promoter (Sax et al. 2002).
R-HSA-6791302 (Reactome) TP53 (p53) binds the promoter of the AIFM2 (AMID) gene, which contains two p53 response elements (Wu et al. 2004).
R-HSA-6791306 (Reactome) TP53 (p53) directly stimulates transcription of the AIFM2 (AMID) gene upon binding to p53 response elements in the promoter of the AIFM2 gene. AIFM2 encodes a mitochondrial outer membrane protein implicated in caspase-independent apoptosis (Wu et al. 2004).
R-HSA-6791323 (Reactome) Binding of TP53 (p53) to p53 response element(s) in the first intron and, possibly, the promoter region of BCL2L14 stimulates transcription of the BCL2L14 gene. BCL2L14 (BCLG) is a BCL2 family member with an unknown function and a proposed but uncertain pro-apoptotic role (Guo et al. 2001, Giam et al. 2012).
R-HSA-6791327 (Reactome) TP53 (p53) binds the p53 response element in the first intron of the BCL2L14 (BCLG) gene. Another p53 response element is found in the promoter region of the BCL2L14 gene but seems to interact with TP53 with low affinity (Miled et al. 2005).
R-HSA-6791348 (Reactome) Once bound to the p53 response element in the promoter of the APAF1 gene, TP53 (p53) stimulates APAF1 transcription (Robles et al. 2001). APAF1 participates in the intrinsic apoptosis pathway, where its interaction with cytochrome C mediates the autocatalytic activation of pro-caspase-9 (Hu et al. 1999).
R-HSA-6791349 (Reactome) TP53 (p53) binds the p53 response element in the promoter of the APAF1 gene (Robles et al. 2001).
R-HSA-6797763 (Reactome) Upon binding to the p53 response element in the promoter of the BIRC5 (survivin) gene, TP53 (p53) inhibits transcription of BIRC5, an inhibitor of apoptosis (Hoffman et al. 2002).
R-HSA-6797766 (Reactome) TP53 (p53) binds the p53 response element in the promoter of the BIRC5 (survivin) gene (Hoffman et al. 2002).
R-HSA-6797993 (Reactome) In hypoxic cells, TP53 (p53) binds p53 responsive elements in the BNIP3L gene. CREBBP (CBP) also localizes to the BNIP3L gene under hypoxic conditions, in vicinity to some of the p53 response elements, which is probably regulated by HIF1A (Fei et al. 2004).
R-HSA-6798004 (Reactome) TP53 (p53) and CREBBP (CBP) bound to the BNIP3L gene stimulate expression of the BNIP3L. BNIP3L is an outer mitochondrial membrane protein that belongs to the BCL2 family and promotes apoptosis of cells under hypoxic stress (Fei et al. 2004).
R-HSA-6798081 (Reactome) Upon binding to the p53 response element in the promoter of the caspase-1 (CASP1) gene, TP53 (p53), TP63 (p63) or TP73 (p73) stimulates transcription of CASP1 (Gupta et al. 2001, Jain et al. 2005, Celardo et al. 2013). CASP1 acts as the interleukin-1 beta (IL1B) converting enzyme (Cerretti et al. 1992) and is involved in the inflammation-related cell death - pyroptosis (Miura et al. 1993, Brough and Rothwell 2007).
R-HSA-6798082 (Reactome) TP53 (p53) (Gupta et al. 2001), TP63 (p63) (Celardo et al. 2013) or TP73 (p73) (Jain et al. 2005) bind the p53 response element in the promoter of the CASP1 (caspase-1) gene.
R-HSA-6798126 (Reactome) Binding of TP53 (p53) to the third intron of the CASP6 (caspase-6) gene stimulates CASP6 expression (MacLachlan and El-Deiry 2002).
R-HSA-6798129 (Reactome) TP53 (p53) binds the p53 response element located in the third intron of the caspase-6 (CASP6) gene (MacLachlan and El-Deiry 2002).
R-HSA-6798138 (Reactome) The CASP10 (caspase-10) gene locus contains multiple p53 response elements that bind TP53 (p53) (Rikhof et al. 2003).
R-HSA-6798139 (Reactome) Upon binding to p53 response elements at the CASP10 (caspase-10) gene locus, TP53 (p53) stimulates CASP10 expression (Rikhof et al. 2003). CASP10 is involved in apoptosis triggered by death receptor signaling (Wang et al. 2001, Sprick et al. 2002).
R-HSA-6798611 (Reactome) TP53 (p53) bound to the p53 response element in the first intron of the TP53AIP1 (p53AIP1) gene stimulates transcription of TP53AIP1. TP53AIP1 protein product localizes to mitochondria and induces apoptosis through dissipation of the mitochondrial membrane potential via an unknown mechanism (Oda et al. 2000). In order to induce TP53AIP1 transcription, TP53 has to be phosphorylated at serine residue S46. DYRK2 kinase is activated by ATM in response to DNA damage and can phosphorylate TP53 at S46 upstream of TP53AIP1 induction (Taira et al. 2007).

The transcription factor ZNF420 (Apak) has a binding site in the first intron of TP53AIP1 that overlaps with the p53 response element. The binding of ZNF420 interferes with the binding of TP53 and results in the repression of TP53AIP1 transcription (Yuan et al. 2012).

R-HSA-6798615 (Reactome) TP53 (p53) phosphorylated at serine residue S46 binds the p53 response element in the first intron of the TP53AIP1 (p53AIP1) gene (Oda et al. 2000).
R-HSA-6798624 (Reactome) The transcription factor ZNF420 (Apak) has a binding site in the first intron of the TP53AIP1 gene that overlaps with the p53 response element. The binding of ZNF420 interferes with the binding of TP53 and results in the repression of TP53AIP1 transcription (Yuan et al. 2012).
R-HSA-6799097 (Reactome) Activated ATM phosphorylates ZNF420 (Apak) at serine residue S68. Phosphorylation at S68 inhibits ZNF420 binding to the first intron of TP53AIP1 (p53AIP1) gene, thus facilitating TP53 (p53)-mediated expression of TP53AIP1 (Yuan et al. 2012). ATM-mediated phosphorylation of ZNF420 also inhibits ZNF420 interaction with TP53 and the consequent TP53 deacetylation (Tian et al. 2009).
R-HSA-6799416 (Reactome) The binding of TP53 (p53) to the p53 response element in the second intron of the TP53INP1 (p53DINP1) gene positively regulates TP53INP1 transcription (Okamura et al. 2001).
R-HSA-6799418 (Reactome) TP53 (p53) binds the p53 response element located in the second intron of the TP53INP1 (p53DINP1) gene (Okamura et al. 2001).
R-HSA-6799441 (Reactome) TP53 (p53) activates transcription of the TP53I3 (PIG3) gene by binding to the pentanucleotide microsatellite sequence in the TP53I3 gene promoter that shares a limited similarity with the consensus p53 response element (Contente et al. 2002). Transcription of the TP53I3 gene can also be activated by p53 family members TP63 (p63) and TP73 (p73) (Bergamaschi et al. 2004). ASPP proteins PPP1R13B (ASPP1) and TP53BP2 (ASPP2) form a complex with p53 family members, leading to increased binding of p53 family members to the TP53I3 promoter and enhanced transcription of TP53I3 (Samuels-Lev et al. 2001, Bergamaschi et al. 2004).
R-HSA-6799462 (Reactome) TP53 (p53) binds a pentanucleotide microsatellite sequence in the promoter of the TP53I3 (PIG3) gene that shares a limited similarity with the consensus sequence of the p53 response element (Contente et al. 2002). TP63 (p63) and TP73 (p73), members of the p53 protein family, can also bind the promoter of TP53I3 (Bergamaschi et al. 2004). Formation of a complex between p53 family members and ASSP proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) enhances binding of TP53 (Samuels-Lev et al. 2001), TP63 or TP73 to the TP53I3 promoter (Bergamaschi et al. 2004).
R-HSA-6799466 (Reactome) TP53I3 (PIG3) forms a homodimer. The dimer interface is formed by two beta strands and an alpha helix of the cofactor-binding domain. Beta strands of the two monomeric subunits are bonded through anti-parallel hydrogen bonds (Porte et al. 2009).
R-HSA-6799722 (Reactome) TP53I3 (PIG3) possesses a NADPH quinone reductase activity, with 1,2-naphthoquinone being its preferred substrate. TP53I3 reduces 1,2-naphthoquinone to a highly unstable semiquinone free radical. Semiquinone reacts with oxygen yielding a quinone and superoxide aninon. Reactive oxygen species (ROS) produced as a result of TP53I3 activity contribute to apoptosis (Porte et al. 2009).
R-HSA-6799733 (Reactome) Semiquinone spontaneously reacts with oxygen to revert to a quinone state and produces superoxide anion (Oppermann 2007, Porte et al. 2009).
R-HSA-6799815 (Reactome) The FAS gene possesses three p53 response elements in the promoter and one p53 response element in its first intron. TP53 family members TP53 (p53), TP63 (p63) and TP73 (p73) can all bind the intronic p53 response element and activate FAS gene transcription. The promoter p53 response elements also contribute to the transcriptional activation of FAS (Schilling et al. 2009). The complex of TP53 (or, probably, TP63 or TP73) with ASSP proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) enhances FAS transcription (Wilson et al. 2013). FAS interacts with its natural ligand, CD95L, a member of the TNF cytokine family, to initiate the death signal cascade, which results in programmed cell death. FAS can function as a guardian against autoimmunity and tumor development (Schilling et al. 2009).
R-HSA-6800001 (Reactome) The p53 family members TP53 (p53), TP63 (p63), or TP73 (p73), most likely in complex with ASPP proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) (Wilson et al. 2013), bind p53 response elements in the first intron and/or promoter of the FAS gene, promoting FAS transcription (Schilling et al. 2009).
R-HSA-6800035 (Reactome) IGFBP3 binds a cell death receptor TMEM219 (IGFBP-3R), a single-span transmembrane protein. Activated TMEM219 can trigger apoptosis, probably by directly binding to and activating caspase-8 (CASP8) (Ingermann et al. 2010).
R-HSA-6800042 (Reactome) TP53 (p53) binds p53 response elements in the first and second introns of the IGFBP3 gene and promotes its upregulation (Buckbinder et al. 1995). In response to DNA damage and hypoxia, IGFBP3 can also be upregulated in a p53-independent manner (Grimberg et al. 2005).
R-HSA-6800044 (Reactome) Binding of TP53 (p53) to p53 response elements in the first and second introns of the IGFBP3 gene upregulates IGFBP3 transcription (Buckbinder et al. 1995). IGFBP3 is one of a family of six homologous proteins that bind IGF1 and IGF2 with high affinity. IGFBP3 contributes to cellular apoptosis in both IGF-dependent and IGF-independent manner (Marzec et al. 2015).
R-HSA-6800250 (Reactome) Binding of TP53 (p53) to the p53 response element in the first intron of the BCL6 gene promotes BCL6 transcription (Margalit et al. 2006). BCL6 is a transcriptional repressor that has been implicated as a facilitator of apoptosis, through inhibition of BCL2 expression (Saito et al. 2009), but also as an inhibitor of apoptosis, through inhibition of TP53 expression (Phan and Dalla-Favera 2004).
R-HSA-6800253 (Reactome) TP53 (p53) binds the p53 response element located in the first intron of the BCL6 gene. This region of the BCL6 gene is frequently subject to translocations, point mutations and deletions in B-cell non-Hodgkin lymphoma (Margalit et al. 2006).
R-HSA-6800279 (Reactome) TP53 (p53) binds an evolutionarily conserved p53 response element in the 5' UTR of the PIDD1 gene (Lin et al. 2000).
R-HSA-6800396 (Reactome) Upon binding to the p53 response element in the 5' UTR of the PIDD1 gene, TP53 (p53) promotes PIDD1 transcription (Lin et al. 2000).
R-HSA-6800490 (Reactome) In response to DNA damage, activated ATM phosphorylates PIDD1 at threonine residue T788, a prerequisite for the subsequent interaction with CRADD (RAIDD) (Ando et al. 2012).
R-HSA-6800793 (Reactome) PIDD1 can localize both to the nucleus and to the cytoplasm. It is not known whether ATM-mediated phosphorylation regulates PIDD1 localization, but PIDDosome formation and caspase-2 activation is thought to be predominantly cytoplasmic (Ando et al. 2012).
R-HSA-6800794 (Reactome) PIDD1 phosphorylated by ATM at threonine residue T788 associates with CRADD (RAIDD), forming a multisubunit structure known as the PIDDosome (Tinel and Tschopp 2004, Ando et al. 2012). The PIDDosome consists of 5 molecules of PIDD1 and 5-7 molecules of CRADD (Nematollahi et al. 2015).
R-HSA-6800797 (Reactome) The PIDDosome promotes activation of CASP2 (caspase-2) by proteolytic cleavage, triggering apoptosis (Tinel and Tschopp 2004). The PIDDosome may also participate in the proteolytic activation of CASP3 and CASP7 (Berube et al. 2005).
R-HSA-6800798 (Reactome) PIDD1, when phosphorylated by ATM at threonine residue T788, associates with CRADD (RAIDD), forming a multisubunit structure known as the PIDDosome (Tinel and Tschopp 2004, Ando et al. 2012). The PIDDosome binds procaspase-2 (CASP2), with CASP2 directly interacting with the CRADD subunit (Tinel and Tschopp 2004).
R-HSA-6800816 (Reactome) Binding of TP53 (p53) or TP63 (p63) to p53 response elements in the promoter and/or the first intron of the PERP gene promotes PERP transcription (Attardi et al. 2000, Ihrie et al. 2005). E2F1 may cooperate with TP53 in the transcriptional activation of PERP (Attardi et al. 2000). PERP is a transmembrane protein that specifically localizes to desmosomes and is important for epithelial integrity. PERP is involved in p53-dependent apoptosis (Attardi et al. 2000, Ihrie et al. 2003) and may act through contributing to caspase activation (Davies et al. 2009).
R-HSA-6800836 (Reactome) The PERP gene possesses two p53 response elements in its promoter region and at least one p53 response element in its first intron, which are involved in the recruitment of TP53 (p53) or TP63 (p63) to the PERP gene locus (Attardi et al. 2000, Ihrie et al. 2005).
R-HSA-6801087 (Reactome) The RABGGTA gene possesses three p53 response elements, one in the promoter and two downstream of the transcription start site. TP53 (p53) can bind, at least, to the promoter p53 response element of the RABGGTA gene (Jen and Cheung 2005).
R-HSA-6801089 (Reactome) Binding of TP53 (p53) to the p53 response element in the promoter of the RABGGTA gene promotes RABGGTA transcription (Jen and Cheung 2005).
R-HSA-6801101 (Reactome) RABGGTA associates with RABGGTB to form RAB geranylgeranyl transferase (RGGT or RAB GGTase). This was initially shown using proteins purified from rat brain (Seabra et al. 1992), but the complex is evolutionarily conserved in human cells (Baron and Seabra 2008).
R-HSA-6801109 (Reactome) RAB escort protein CHM (REP1) binds the RAB geranylgeranyl transferase complex, RGGT, composed of RABGGTA and RABGGTB (Baron and Seabra 2008). The interaction between CHM and the RGGT complex is enhanced by the presence of phosphoisoprenoids (Thoma et al. 2001). The complex of RGGT and CHM catalyzes geranylgeranylation of small GTPases RAB1A, RAB3A and RAB5A, which is needed for the membrane localization of RABs (Farnsworth et al. 1994). RAB geranylgeranyl transferase can play an anti-apoptotic role, through an unknown mechanism (Lackner et al. 2005). RAB5A, the substrate of RGGT:CHM complex, was shown to positively regulate formation of autophagosomes (Li et al. 2013).
R-HSA-6801166 (Reactome) TP53 (p53) binds the p53 response element in the promoter of the STEAP3 (TSAP6) gene (Passer et al. 2003).
R-HSA-6801184 (Reactome) Binding of TP53 (p53) to the p53 response element in the promoter of the STEAP3 (TSAP6) gene promotes STEAP3 transcription (Passer et al. 2003). Tumor suppressor-activated pathway 6 (TSAP6) was initially discovered as differentially regulated following p53 activation and was later shown to be strongly activated in tumor suppression and reversion, and was hence named TSAP6. TSAP6 knockdown results in inhibition of apoptosis. TSAP6 binds to and cooperates with BNIP3L (NIX), a pro-apoptotic BH3-only BCL2-family member, and MYT1 kinase, a negative regulator of the G2/M transition (Lespagnol et al. 2008).
R-HSA-6801195 (Reactome) STEAP3 (TSAP6) forms a complex with a pro-apoptotic protein BNIP3L (NIX) and cooperates with BNIP3L in promoting apoptosis, but the exact mechanism is not known (Passer et al. 2003).

While STEAP3 localizes to endosome membranes, BNIP3L localizes to the outer mitochondrial membrane. BNIP3L has recently been implicated in the relocalization of endo-lysosomes to inner mitochondrial compartments, which can play a role in endo-lysosomal processing of mitochondria (Hamacher-Brady et al. 2014).

R-HSA-6801209 (Reactome) TP53 (p53) binds the p53 response element in the second exon of the TRIAP1 (p53CSV) gene (Park and Nakamura 2005).
R-HSA-6801213 (Reactome) Binding of TP53 (p53) to the p53 response element in the second intron of the TRIAP1 (TP53-regulated inhibitor of apoptosis, also known as p53 survival factor or p53CSV) gene induces TRIAP1 transcription (Park and Nakamura 2005). Recently, TRIAP1 has been characterized as a gene-specific repressor of p21 (CDKN1A). TRIAP1 knockdown leads to augmented p21 expression before and during p53 activation and thus slows down cell proliferation (Andrysik et al. 2013).
R-HSA-6801242 (Reactome) In the mitochondrial intermembrane space, TRIAP1 forms a complex with PRELID1 (PRELI) (Potting et al. 2013).
R-HSA-6801250 (Reactome) The complex of TRIAP1 and PRELID1 (TRIAP1:PRELID1) facilitates transport of phosphatidic acid (PA) from the outer mitochondrial membrane to the inner mitochondrial membrane. At the inner mitochondrial membrane, the PA is used for the synthesis of cardiolipin (CL). CL prevents the release of cytochrome C from mitochondria, thus playing an anti-apoptotic role (Potting et al. 2013).
R-HSA-6801355 (Reactome) TP53 (p53) binds the p53 response element in the promoter of the NLRC4 (Ipaf) gene (Sadasivam et al. 2005).
R-HSA-6801415 (Reactome) The binding of TP53 (p53) to the p53 response element in the promoter of the NLRC4 (Ipaf) gene promotes NLRC4 transcription. NLRC4 is an activator of caspase-1 (CASP1) (Poyet et al. 2001), which is also a TP53 target. NLRC4 and CASP1 play an important role in innate immunity via inflammasome-mediated destruction of pathogenic bacteria and fungi (Schroder and Tschopp 2010). NLRC4 contributes to cell death (Sadasivam et al. 2005), possibly through interleukin-1-mediated pyroptosis (Brough and Rothwell 2007).
RABGGTA GeneR-HSA-6801087 (Reactome)
RABGGTA GeneR-HSA-6801089 (Reactome)
RABGGTAArrowR-HSA-6801089 (Reactome)
RABGGTAR-HSA-6801101 (Reactome)
RABGGTBR-HSA-6801101 (Reactome)
RGGT:CHMArrowR-HSA-6801109 (Reactome)
RGGTArrowR-HSA-6801101 (Reactome)
RGGTR-HSA-6801109 (Reactome)
STEAP3 GeneR-HSA-6801166 (Reactome)
STEAP3 GeneR-HSA-6801184 (Reactome)
STEAP3:BNIP3LArrowR-HSA-6801195 (Reactome)
STEAP3ArrowR-HSA-6801184 (Reactome)
STEAP3R-HSA-6801195 (Reactome)
TMEM219R-HSA-6800035 (Reactome)
TNFRSF10A,

TNFRSF10B, TNFRSF10C,

TNFRSF10D
ArrowR-HSA-5633441 (Reactome)
TNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10D GenesR-HSA-5633414 (Reactome)
TNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10D GenesR-HSA-5633441 (Reactome)
TP53AIP1 GeneR-HSA-6798611 (Reactome)
TP53AIP1 GeneR-HSA-6798615 (Reactome)
TP53AIP1 GeneR-HSA-6798624 (Reactome)
TP53AIP1ArrowR-HSA-6798611 (Reactome)
TP53I3 DimerArrowR-HSA-6799466 (Reactome)
TP53I3 Dimermim-catalysisR-HSA-6799722 (Reactome)
TP53I3 GeneR-HSA-6799441 (Reactome)
TP53I3 GeneR-HSA-6799462 (Reactome)
TP53I3ArrowR-HSA-6799441 (Reactome)
TP53I3R-HSA-6799466 (Reactome)
TP53INP1 GeneR-HSA-6799416 (Reactome)
TP53INP1 GeneR-HSA-6799418 (Reactome)
TP53INP1ArrowR-HSA-6799416 (Reactome)
TRIAP1 GeneR-HSA-6801209 (Reactome)
TRIAP1 GeneR-HSA-6801213 (Reactome)
TRIAP1:PRELID1ArrowR-HSA-6801242 (Reactome)
TRIAP1:PRELID1mim-catalysisR-HSA-6801250 (Reactome)
TRIAP1ArrowR-HSA-6801213 (Reactome)
TRIAP1R-HSA-6801242 (Reactome)
ZNF420:TP53AIP1 GeneArrowR-HSA-6798624 (Reactome)
ZNF420:TP53AIP1 GeneTBarR-HSA-6798611 (Reactome)
ZNF420R-HSA-6798624 (Reactome)
ZNF420R-HSA-6799097 (Reactome)
p-S15,S20,S46-TP53

Tetramer:TP53AIP1

Gene
ArrowR-HSA-6798611 (Reactome)
p-S15,S20,S46-TP53

Tetramer:TP53AIP1

Gene
ArrowR-HSA-6798615 (Reactome)
p-S15,S20,S46-TP53 TetramerR-HSA-6798615 (Reactome)
p-S15,S20-TP53 Tetramer:AIFM2 GeneArrowR-HSA-6791302 (Reactome)
p-S15,S20-TP53 Tetramer:AIFM2 GeneArrowR-HSA-6791306 (Reactome)
p-S15,S20-TP53 Tetramer:APAF1 GeneArrowR-HSA-6791348 (Reactome)
p-S15,S20-TP53 Tetramer:APAF1 GeneArrowR-HSA-6791349 (Reactome)
p-S15,S20-TP53

Tetramer:BCL2L14

Gene
ArrowR-HSA-6791323 (Reactome)
p-S15,S20-TP53

Tetramer:BCL2L14

Gene
ArrowR-HSA-6791327 (Reactome)
p-S15,S20-TP53 Tetramer:BCL6 GeneArrowR-HSA-6800250 (Reactome)
p-S15,S20-TP53 Tetramer:BCL6 GeneArrowR-HSA-6800253 (Reactome)
p-S15,S20-TP53 Tetramer:BID GeneArrowR-HSA-6791285 (Reactome)
p-S15,S20-TP53 Tetramer:BID GeneArrowR-HSA-6791291 (Reactome)
p-S15,S20-TP53 Tetramer:BIRC5 GeneArrowR-HSA-6797766 (Reactome)
p-S15,S20-TP53 Tetramer:BIRC5 GeneTBarR-HSA-6797763 (Reactome)
p-S15,S20-TP53

Tetramer:CASP10

Gene
ArrowR-HSA-6798138 (Reactome)
p-S15,S20-TP53

Tetramer:CASP10

Gene
ArrowR-HSA-6798139 (Reactome)
p-S15,S20-TP53 Tetramer:CASP6 GeneArrowR-HSA-6798126 (Reactome)
p-S15,S20-TP53 Tetramer:CASP6 GeneArrowR-HSA-6798129 (Reactome)
p-S15,S20-TP53 Tetramer:CREBBP:BNIP3L GeneArrowR-HSA-6797993 (Reactome)
p-S15,S20-TP53 Tetramer:CREBBP:BNIP3L GeneArrowR-HSA-6798004 (Reactome)
p-S15,S20-TP53

Tetramer:IGFBP3

Gene
ArrowR-HSA-6800042 (Reactome)
p-S15,S20-TP53

Tetramer:IGFBP3

Gene
ArrowR-HSA-6800044 (Reactome)
p-S15,S20-TP53 Tetramer:NDRG1 GeneArrowR-HSA-5633295 (Reactome)
p-S15,S20-TP53 Tetramer:NDRG1 GeneArrowR-HSA-5633314 (Reactome)
p-S15,S20-TP53 Tetramer:PIDD1 GeneArrowR-HSA-6800279 (Reactome)
p-S15,S20-TP53 Tetramer:PIDD1 GeneArrowR-HSA-6800396 (Reactome)
p-S15,S20-TP53

Tetramer:PMAIP1

Gene
ArrowR-HSA-140214 (Reactome)
p-S15,S20-TP53

Tetramer:PMAIP1

Gene
ArrowR-HSA-4331331 (Reactome)
p-S15,S20-TP53

Tetramer:RABGGTA

Gene
ArrowR-HSA-6801087 (Reactome)
p-S15,S20-TP53

Tetramer:RABGGTA

Gene
ArrowR-HSA-6801089 (Reactome)
p-S15,S20-TP53

Tetramer:STEAP3

Gene
ArrowR-HSA-6801166 (Reactome)
p-S15,S20-TP53

Tetramer:STEAP3

Gene
ArrowR-HSA-6801184 (Reactome)
p-S15,S20-TP53 Tetramer:TNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10D GenesArrowR-HSA-5633414 (Reactome)
p-S15,S20-TP53 Tetramer:TNFRSF10A,TNFRSF10B,TNFRSF10C,TNFRSF10D GenesArrowR-HSA-5633441 (Reactome)
p-S15,S20-TP53

Tetramer:TP53INP1

Gene
ArrowR-HSA-6799416 (Reactome)
p-S15,S20-TP53

Tetramer:TP53INP1

Gene
ArrowR-HSA-6799418 (Reactome)
p-S15,S20-TP53

Tetramer:TRIAP1

Gene
ArrowR-HSA-6801209 (Reactome)
p-S15,S20-TP53

Tetramer:TRIAP1

Gene
ArrowR-HSA-6801213 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-4331331 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-5633295 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-5633414 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6791285 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6791302 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6791327 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6791349 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6797766 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6797993 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6798129 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6798138 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6799418 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6800042 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6800253 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6800279 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6801087 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6801166 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6801209 (Reactome)
p-S15,S20-TP53 TetramerR-HSA-6801355 (Reactome)
p-S15,S20-TP53,TP63,TP73R-HSA-6798082 (Reactome)
p-S15,S20-TP53,TP63R-HSA-6800836 (Reactome)
p-S15,S20-TP53:NLRC4 GeneArrowR-HSA-6801355 (Reactome)
p-S15,S20-TP53:NLRC4 GeneArrowR-HSA-6801415 (Reactome)
p-S1981,Ac-K3016-ATMmim-catalysisR-HSA-6799097 (Reactome)
p-S1981,Ac-K3016-ATMmim-catalysisR-HSA-6800490 (Reactome)
p-S68-ZNF420ArrowR-HSA-6799097 (Reactome)
p-T788-PIDD1ArrowR-HSA-6800490 (Reactome)
p-T788-PIDD1ArrowR-HSA-6800793 (Reactome)
p-T788-PIDD1R-HSA-6800793 (Reactome)
p-T788-PIDD1R-HSA-6800794 (Reactome)
phosphatidic acidArrowR-HSA-6801250 (Reactome)
semiquinoneArrowR-HSA-6799722 (Reactome)
semiquinoneR-HSA-6799733 (Reactome)

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